Cyclosporine in Combination With Carfilzomib and Dexamethasone in Relapsed Multiple Myeloma Refractory to Carfilzomib and High Expression of PPIA Gene in Myeloma Cells

NCT04813653 | Completed Phase 1 DMC

• 1 other identifier: 1007-20-TLV
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1, open-label, single-arm, prospective, single center study will evaluate the safety, tolerability and efficacy of cyclosporine in combination with carfilzomib and dexamethasone in patients with relapsed and refractory multiple myeloma (RRMM).

Conditions

Multiple Myeloma in Relapse; Multiple Myeloma, Refractory

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment parameters.

  Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment parameters.

  follow-up 2 years post study

Secondary Outcomes (11)

• Overall response rate ORR

  follow-up 2 years post study

• Progression free survival PFS

  follow-up 2 years post study

• Duration of Response DOR

  follow-up 2 years post study

• Time to Response TTR

  follow-up 2 years post study

• Depth of Best Response (DpR)

  follow-up 2 years post study

Study Arms (1)

cyclosporine in combination with carfilzomib and dexamethasone

EXPERIMENTAL

cyclosporine in combination with carfilzomib and dexamethasone in patients with relapsed multiple myeloma refractory to carfilzomib with high expression of the PPIA gene in myeloma cells

Drug: cyclosporine in combination with carfilzomib and dexamethasone

Interventions

cyclosporine in combination with carfilzomib and dexamethasone DRUG

patients will be treated with cyclosporine with dose titration based on repeated determinations of whole blood concentrations to achieve a target trough concentration of 250 ng/mL, in combination with carfilzomib plus dexamethasone.

cyclosporine in combination with carfilzomib and dexamethasone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female patients, 18 years of age or older.
• Multiple myeloma diagnosed according to standard IMWG criteria.
• Patients must have measurable disease defined by at least one of the following three measurements:
• Serum M-protein 1 g/dL (10 g/L).
• Urine M-protein 200 mg/24 hours.
• Serum free light chain assay: involved free light chain level at least 100 mg/L, provided that the serum free light chain ratio is abnormal.
• Patients received one or two prior lines of therapy which must have included bortezomib, lenalidomide-and daratumumab.
• Patient received carfilzomib-based therapy either as their most recent line of therapy and within 3 months from study enrolment, and either failed to achieve a minor response after completing 2 cycles of carfilzomib based therapy, or are refractory to treatment.
• Patients were found to have a high-expression level of PPIA, \>1.2 unique RNA molecules (UMI) per cell on average, by scRNA sequencing of their myeloma cells from bone marrow aspiration sample at study screening.
• Patients must meet the following clinical laboratory criteria:
• Absolute neutrophil count (ANC) ≥1,000/mm3 and platelet count≥75,000/mm3. Platelet transfusions to help patients meet eligibility criteria are not allowed within 3 days of enrolment.
• Total bilirubin ≤1.5 the upper limit of the normal range (ULN).
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 ULN.
• Calculated creatinine clearance ≥45 mL/min
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2.

You may not qualify if:

• Patient underwent an allogeneic transplantation.
• Major surgery within 14 days before enrolment.
• Central nervous system involvement
• Concomitant use of any other antineoplastic treatment with activity against MM (with the exception of ≤40 mg Dexamethasone per day or equivalent for no longer than 4 days).
• Anti-myeloma therapy as follows prior to screening bone marrow aspiration:
• Targeted therapy, within 14 days or at least 5 half-lives, whichever is less;
• Monoclonal antibody treatment for multiple myeloma within 21 days;
• Cytotoxic therapy within 14 days;
• Proteasome inhibitor therapy within 14 days; note: no window is required for carfilzomib
• Immunomodulatory agent therapy within 7 days.
• Radiotherapy within 14 days (with the exception of radiotherapy for spinal cord compression or for pain control that should be discussed and approved by the sponsor- investigator prior to study enrolment). However, if the radiation portal covered ≤5% of the bone marrow reserve, the subject is eligible irrespective of the end date of radiotherapy.
• Diagnosed or treated for another malignancy within 2 years before enrolment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
• Moderate to severe kidney injury (Calculated creatinine clearance ≤45 mL/min).
• Severe liver disease (cirrhosis grade Child-Pugh B or C; significant hepatocellular or cholestatic liver injury).
• Diagnosis of Waldenstrom's macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome, plasma cell leukaemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome.

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead
• Weizmann Institute of Science: collaborator

Study Sites (1)

Tel Aviv Sourasky Medical Center

Tel Aviv, Israel

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Cyclosporine; carfilzomib; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Study Officials

• Yael Cohen, MD

  TASMC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: single-arm, prospective study

Study Record Dates

• First Submitted: March 18, 2021
• First Posted: March 24, 2021
• Study Start: April 18, 2021
• Primary Completion: March 5, 2025
• Study Completion: March 5, 2025
• Last Updated: July 24, 2025

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)